Unobstructed Coronary Arteries Research Articles

Comparing Pressure-Bounded Versus Thermodilution-Derived Coronary Flow Reserve in Unobstructed Coronary Arteries

Comparing Pressure-Bounded Versus Thermodilution-Derived Coronary Flow Reserve in Unobstructed Coronary Arteries

Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm.

Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing. A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n = 119) and microvascular CAS (n = 87). Patients with a negative ACh test result (n = 45) served as controls. We found no association below the genome-wide significance threshold of p < 5 × 10-8, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p < 10-05) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p = 0.01). In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. Nine-hundred-seventeen coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22-50] vs 29 [21-41], p<0.001) was significantly higher and QFR (0.92 [0.78-0.99] vs 0.97 [0.91-0.99], p<0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (AUCROC 0.632 [95% CI 0.589-0.674], p<0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669-0.784], p<0.0001, p-value for AUCROC comparison=0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p-value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Myocardial perfusion in cardiac amyloidosis.

Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Abstract 13882: Myocardial Hypoperfusion in Severe Aortic Stenosis is Reversed by Aortic Valve Replacement

Background: Myocardial hypoperfusion in severe aortic stenosis (AS) without obstructive coronary disease may be secondary to hemodynamic influences (and therefore readily reversible by aortic valve replacement[AVR]) or structural alterations in the left ventricle (LV) such as increased mass and reduction in capillary density. Aim: To evaluate the early effect of AVR on myocardial blood flow (MBF) in patients with severe symptomatic AS without flow-limiting coronary artery disease. Methods: Prospective case-control study of severe symptomatic AS without obstructive coronary disease referred for surgical or transcatheter AVR and propensity matched to a control cohort with unobstructed coronary arteries. Patients underwent adenosine stress cardiovascular magnetic resonance at baseline and 8-weeks (median) post-operatively. Histology from 9 myocardial septal biopsies taken at AVR were compared against necropsy controls (n=5). Results: 52 patients were included; 26 with severe AS (median [IQR] age 71[66-75], 73% male) and 26 age, sex and co-morbidity matched controls. In AS, peak velocity(Vmax) was 4.3m/s[4.1-4.5] and AVA 0.8cm 2 [0.6-0.9]. AS patients had greater LV mass and late gadolinium enhancement. AS patients had lower stress MBF than controls (1.63ml/g/min[1.38-2.08] vs 2.13[1.76-2.52], p=0.003) which increased to 1.97ml/g/min after AVR (p=0.7 post-AVR vs. Controls). This was driven by a 40% increase in subendocardial MBF (1.26ml/g/min[1.18-1.78] to 1.77[1.62-2.32]). Capillary density was reduced almost threefold in AS (495/mm 2 [407-686] vs 1376[1208-1579], p&lt;0.001). Conclusions: Severe AS results in subendocardial hypoperfusion which is rapidly improved after AVR. There is a threefold reduction in capillary density, however factors related to elevated afterload (which is reduced by AVR) are the most influential.

Myocardial Tissue Characterization in Patients with Hypertensive Crisis, Positive Troponin, and Unobstructed Coronary Arteries: A Cardiovascular Magnetic Resonance-Based Study.

Hypertensive crisis can present with cardiac troponin elevation and unobstructed coronary arteries. We used cardiac magnetic resonance (CMR) imaging to characterize the myocardial tissue in patients with hypertensive crisis, elevated cardiac troponin, and unobstructed coronary arteries. Patients with hypertensive crisis and elevated cardiac troponin with coronary artery stenosis <50% were enrolled. Patients with troponin-negative hypertensive crisis served as controls. All participants underwent CMR imaging at 1.5 Tesla. Imaging biomarkers and tissue characteristics were compared between the groups. There were 19 patients (63% male) with elevated troponin and 24 (33% male) troponin-negative controls. The troponin-positive group was older (57 ± 11 years vs. 47 ± 14 years, p = 0.015). The groups had similar T2-weighted signal intensity ratios and native T1 times. T2 relaxation times were longer in the troponin-positive group, and the difference remained significant after excluding infarct-pattern late gadolinium enhancement (LGE) from the analysis. Extracellular volume (ECV) was higher in the troponin-positive group (25 ± 4 ms vs. 22 ± 3 ms, p = 0.008) and correlated strongly with T2 relaxation time (rs = 0.701, p = 0.022). Late gadolinium enhancement was 32% more prevalent in the troponin-positive group (82% vs. 50%, p = 0.050), with 29% having infarct-pattern LGE. T2 relaxation time was independently associated with troponin positivity (OR 2.1, p = 0.043), and both T2 relaxation time and ECV predicted troponin positivity (C-statistics: 0.71, p = 0.009; and 0.77, p = 0.006). Left ventricular end-diastolic and left atrial volumes were the strongest predictors of troponin positivity (C-statistics: 0.80, p = 0.001; and 0.82, p < 0.001). The increased T2 relaxation time and ECV and their significant correlation in the troponin-positive group suggest myocardial injury with oedema, while the non-ischaemic LGE could be due to myocardial fibrosis or acute necrosis. These CMR imaging biomarkers provide important clinical indices for risk stratification and prognostication in patients with hypertensive crisis.

CMR reclassifies the majority of patients with suspected MINOCA and non MINOCA.

In ∼5-15% of all cases of acute coronary syndromes (ACS) have unobstructed coronaries on angiography. Cardiac magnetic resonance (CMR) has proven useful to identify in most patients the underlying diagnosis associated with this presentation. However, the role of CMR to reclassify patients from the initial suspected condition has not been clarified. The aim of this study was to assess the proportion of patients with suspected MINOCA, or non-MINOCA, that CMR reclassifies with an alternative diagnosis from the original clinical suspicion. A retrospective cohort of patients in a tertiary cardiology centre was identified from a registry database. Patients who were referred for CMR for investigation of suspected MINOCA, and a diagnosis pre- and post-CMR was recorded to determine the proportion of diagnoses reclassified. A total of 888 patients were identified in the registry. CMR reclassified diagnosis in 78% of patients. Diagnosis of MINOCA was confirmed in only 243 patients (27%), whilst most patients had an alternative diagnosis (73%): myocarditis n = 217 (24%), Takotsubo syndrome n = 115 (13%), cardiomyopathies n = 97 (11%), and normal CMR/non-specific n = 216 (24%). In a large single-centre cohort of patients presenting with ACS and unobstructed coronary arteries, most patients had a non-MINOCA diagnosis (73%) (myocarditis, Takotsubo, cardiomyopathies, or normal CMR/non-specific findings), whilst only a minority had confirmed MINOCA (27%). Performing CMR led to reclassifying patients' diagnosis in 78% of cases, thus confirming its important clinical role and underscoring the clinical challenge in diagnosing MINOCA and non MINOCA conditions.

Prognostic Value of Cardiac Magnetic Resonance Imaging in Patients With a Working Diagnosis of MINOCA-An Outcome Study With up to 10 Years of Follow-Up.

Patients with a working diagnosis of myocardial infarction with unobstructed coronary arteries (MINOCA) represent a heterogeneous cohort. The prognosis could vary substantially depending on the underlying cause. Although cardiac magnetic resonance (CMR) is considered a key diagnostic tool in these patients, there are limited data linking the CMR diagnosis with the outcome. This study is a prospective outcomes registry of consecutive patients presenting with a working diagnosis of MINOCA who were clinically referred for CMR at an academic hospital from October 2003 to February 2020. We assessed the relationships between the prespecified CMR diagnoses of acute myocardial infarction (AMI), myocarditis, nonischemic cardiomyopathy (NICM), normal CMR study, and major adverse cardiac events (MACEs). Of 252 patients, the CMR diagnosis was AMI in 63 (25%), myocarditis in 33 (13%), NICM in 111 (44%), normal CMR in 37 (15%), and other diagnoses in 8 (3%). A specific nonischemic cause was diagnosed allowing true MINOCA to be ruled-out in 57% of the cohort. During up to 10 years of follow-up (1595 patient-years), MACE occurred in 84 patients (33%), which included 64 deaths (25%). The unadjusted cumulative 10-year rate of MACE was 47% in AMI, 24% in myocarditis, 50% in NICM, and 3.5% in patients with a normal CMR (Log-rank P<0.001). The CMR diagnosis provided incremental prognostic value over clinical factors including age, gender, coronary artery disease risk factors, presentation with ST-elevation, and peak troponin (incremental χ² 17.9, P<0.001); and patients with diagnoses of AMI, myocarditis, and NICM had worse MACE-free survival than patients with a normal CMR. In patients with a working diagnosis of MINOCA, CMR allows ruling-out true MINOCA in over half of the patients. CMR diagnoses of AMI, myocarditis, and NICM are associated with worse MACE-free survival, whereas a normal CMR study portends a benign prognosis.

Infarct-like versus Non-Infarct-like Clinical Presentation of Acute Myocarditis: Comparison of Cardiac Magnetic Resonance (CMR) Findings.

The clinical presentation of acute myocarditis (AM) is widely variable, ranging from a subclinical disease to an infarct-like syndrome. Cardiac magnetic resonance (CMR) has become the reference non-invasive diagnostic tool for suspected AM, allowing the identification of the various hallmarks of myocardial inflammation (edema, fibrosis, and hyperemia). The aim of the study was to investigate any differences in morphological, functional, and tissue characterization CMR parameters between infarct-like AM in patients with unobstructed coronary arteries and non-infarct-like AM, diagnosed according to the original Lake-Louise Criteria (LLC); Methods: We retrospectively selected 39 patients diagnosed with AM according to LLC, divided into 2 groups according to the clinical presentation: infarct-like in group 1 patients and non-infarct-like in group 2 patients. CMR morphologic, functional, and tissue characterization parameters were analyzed and compared. In group 1, CMR tissue characterization parameters were mainly altereda in septal location with mesocardial myocardial involvement; in group 2, CMR tissue characterization parameters were mainly altered in a lateral location with subepicardial myocardial involvement mainly at the mid-cavity. No significant differences in morphological or functional parameters were observed between the two study groups. Our results showed differences in the localization and distribution of myocardial tissue damage assessed by CMR among forms of AM accompanied by an infarct-like clinical presentation compared with non-infarct-like presentations of AM. The mechanisms underlying the different preferential sites of damage observed in our study are not known, and we do not exclude the possibility of their prognostic implications.

CMR access for patients with chest pain, raised troponins and unobstructed coronary arteries. A retrospective real world analysis from a large UK district general hospital

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The differential diagnosis in patients with chest pain, a dynamic troponin rise and unobstructed coronary arteries is broad. Cardiac magnetic resonance (CMR) imaging can differentiate between the aetiologies of myocardial injury The UK has a low number of MR scanners/million people compared to Germany (8.6 v 34.4) resulting in poor equity in access to CMR (1). Our hospital relies on an off-site private health care provider for the CMR service. Background The 2020 ESC Taskforce guidelines recommend the use CMR in all myocardial infarction with normal coronary artery (MINOCA ) patients ideally within 2 weeks. Purpose There were three objectives: 1. To identify what proportion of these patients had a CMR scan 2. To determine the mean CMR waiting time 3. To establish in how many cases CMR changed the diagnosis and patient management. Methods We retrospectively collected the data from January - December 2021 of all patients admitted to our hospital with chest pain, a dynamic troponin rise and unobstructed coronary arteries on coronary angiography. Patient demographics, troponin levels, the discharge diagnosis, timing and details of CMR study and changes in diagnosis and management post CMR scan were recorded. Results 81 patients fit inclusion criteria (49% male, mean 61.2±14.8 years). Mean troponin rise 271±403 ng/L. 45% underwent CMR imaging. Mean waiting time for CMR 35 ± 26.9 days. 21% had CMR in &amp;lt; 14 days. CMR scan led to a change in diagnosis in 40% and changed management in 29.7%. In 37.5 % of patients with a pre-scan diagnosis of myocarditis were found to have myocardial infarction post CMR scan. Conclusion The majority (55%) of our MINOCA patients did not have CMR imaging and the minority had it in &amp;lt; 2 weeks. As CMR led to a management change in almost one third of patients there is no doubt that our patients are getting suboptimal care due to lack of timely access to CMR. This study shows the difficulties of implementing guidelines in the real world particularly in a UK hospital where resources are strained and rapid expansion of urgent CMR slots is not possible.

Coronary Spasm: Ethnic and Sex Differences.

Coronary spasm (CS), which may occur at the epicardial (focal or diffuse spasm) and/or microvascular (microvascular spasm) level, is a well-established cause of myocardial ischaemia, in particular in patients with anginal chest pain despite unobstructed coronary arteries. The diagnosis of CS can be confirmed during coronary angiography by an additional provocation test with vasoactive substances such as acetylcholine. Due to partially inconsistent data from large clinical studies, especially between Asian and white CS patients, ethnic differences concerning the prevalence and angiographic patterns of CS seem to exist. Furthermore, several studies in patients with coronary vasomotor disorders pointed towards differences among male and female CS patients. This article gives an overview of ethnic- and sex-related differences in patients with CS.

A changing heart in tako-tsubo syndrome.

A 63-year-old female presented with acute chest pain and ECG showing T wave inversion in the anterior and inferior leads. Troponin T (TnT) was significantly elevated (peak 1378 ng/L; normal <14 ng/L), as was NT-proBNP (3091 ng/L; normal <400 ng/L). Invasive angiography showed unobstructed coronary arteries with mid-ventricular ballooning and hypokinesia on ventriculography (see Supplementary data online, Video S1) and echocardiography (see Supplementary data online, Video S2), suggesting a mid-ventricular tako-tsubo syndrome (TTS). Cardiac magnetic resonance (CMR) was booked but the patient was unable to attend. Focussed history using the InterTAK diagnostic score assessment revealed no emotional or physical triggers. The patient re-presented six months later with similar symptoms and elevated TnT. Inpatient echocardiography showed a reverse TTS pattern (see Supplementary data online, Video S3) and CMR at 1.5T showed basal hypokinesia with matching elevated native T1 (1220 ms; normal 950–1100 ms) and T2 (69 ms; normal <48 ms) (Panels A–B). Quantitative perfusion maps following adenosine stress perfusion to investigate microvascular disease showed basal to mid circumferential hypoperfusion with normal apical myocardial blood flow, not suggestive of specific coronary artery territory ischaemia (Panel D) and no late gadolinium enhancement (LGE) (Panel C), confirming a reverse TTS. The patient further presented two months later with chest pain and TnT elevation. Repeat inpatient CMR on this occasion showed a classic TTS pattern with apical hypokinesia and elevated T1 and T2 (1261 ms and 81 ms, respectively) at the mid to apical segments with no LGE (Panels E–G). The case was further explored but no triggers, including neurological or psychiatric abnormalities were found. Recurrent TTS with different phenotypes has previously been described but is rare, especially without a trigger. Our case illustrates the utility of multimodality imaging in the investigation of TTS; in particular, multiparametric tissue mapping by CMR. Furthermore, the novel quantitative perfusion maps characterising myocardial blood flow added diagnostic utility.

Bilateral subclavian artery occlusion masking severe systemic hypertension as cause for heart failure: the role of multi-modality cardiovascular imaging in guiding diagnosis and management.

A 62-year-old female smoker presented with gradually worsening exertional breathlessness over 1 year, despite initiation of treatment for chronic obstructive pulmonary disease. She gave a history of transient ischaemic attack and possible subclavian artery stenosis diagnosed at a different institution. Physical examination revealed blood pressure (BP) readings of 80/50 mmHg in both arms. Electrocardiogram showed sinus rhythm with left bundle branch block (QRS duration 147 ms, Panel A). Echocardiography identified severe left ventricular (LV) systolic dysfunction (ejection fraction 29%) and suspected apical thrombus (Panel B, Supplementary data online, Video S1). She was initiated on ivabradine and considered for cardiac resynchronization therapy due to hypotension which limited the introduction of additional heart failure (HF) pharmacotherapy. Cardiovascular magnetic resonance confirmed LV dysfunction (supplementary data online, Video S2) and mild LV hypertrophy. There was septal fibrosis but no myocardial infarction or LV thrombus (Panel C & D), suggestive of non-ischaemic dilated cardiomyopathy phenotype. Computed tomography coronary angiography showed unobstructed coronary arteries but revealed bilateral subclavian artery occlusion (Panels E–G).

Coronary Slow Flow Is Not Diagnostic of Microvascular Dysfunction in Patients With Angina and Unobstructed Coronary Arteries.

Background Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC) 27, can diagnose coronary microvascular dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED. Methods and Results Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, adenosine-mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve <2.5) and CED in response to acetylcholine (acetylcholine flow reserve ≤1.5); 152 patients underwent assessment using adenosine, of whom 82 underwent further acetylcholine testing. Forty-six patients (30%) had CSFP, associated with lower flow velocity and higher microvascular resistance as compared with controls (16.56.9 versus 20.26.9 cm/s; P=0.001 and 6.261.83 versus 5.361.83 mm Hg/cm/s; P=0.009, respectively). However, as a diagnostic test, CSFP had poor sensitivity and specificity for both CMD (26.7% and 65.2%) and CED (21.1% and 56.0%). Furthermore, on receiver operating characteristics analyses, CTFC could not predict CMD or CED (area under the curve, 0.41 [95% CI, 0.32%-0.50%] and 0.36 [95% CI, 0.23%-0.49%], respectively). Conclusions In patients with angina and nonobstructed coronary arteries, CSFP and CTFC are not diagnostic of CMD or CED. Guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited.

Proof of concept study on coronary microvascular function in low flow low gradient aortic stenosis

ObjectivesWe hypothesised that low flow low gradient aortic stenosis (LFLGAS) is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is...

Case Series of Triathletes with Takotsubo Cardiomyopathy Presenting with Swimming-Induced Pulmonary Edema.

To report three cases of triathletes who presented with swimming-induced pulmonary edema (SIPE) following water immersion. They were subsequently diagnosed with Takotsubo cardiomyopathy (TCM). Retrospective case series. All cases were recreational athletes competing in mass participation triathlons between June 2018 and 2019. They were initially managed by the event medical team and subsequently at the local tertiary level hospital. Written consent was gained from all the subjects. The three triathletes were aged between 50 and 60 years, two were females, and all presented with acute dyspnoea on exiting the water. Two also presented with chest pain and haemoptysis. A diagnosis of SIPE was suspected by the medical event team on initial presentation of low oxygen saturations and clinical signs of pulmonary oedema. All were transferred to the local emergency department and had signs of pulmonary oedema on chest radiographs. Further investigations led to a diagnosis of TCM with findings of T wave inversion in anterolateral electrocardiogram leads and apical hypokinesia on transthoracic echocardiogram and unobstructed coronary arteries. This case series presents triathletes diagnosed with SIPE and TCM following the open water swim phase. It is unclear whether the myocardial dysfunction contributed to causation of SIPE or was the result of SIPE. Mass participation race organizers must be prepared that both SIPE and TCM can present in this population. Those presenting with an episode of SIPE require prompt evaluation of their cardiac and pulmonary physiology. Further research is required to ascertain the exact nature of the relationship between TCM and SIPE.

Myocardial ischaemia in cardiac amyloidosis: a change of perspective

Abstract Introduction Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis; however many clinical observations are not explained by the concept of replacement of the interstitium by amyloid material. Preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. Purpose This study assesses the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. Methods Ninety-two patients with cardiac amyloidosis (CA) (AL = 41, ATTR = 51) and 97 without CA (3-vessel coronary disease (3VD) = 47, unobstructed coronary arteries = 26, healthy volunteers (HV) = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-six myocardial biopsies and 3 explanted hearts with CA were analysed histopathologically. Results Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA = 1.03±0.51 ml/min/g, 3VD = 1.35±0.50 ml/min/g, Unobstructed coronaries = 2.92±0.52 ml/min/g, HV = 3.14±0.69 ml/min/g; CA vs 3VD p=0.008, CA vs Unobstructed coronaries p&amp;lt;0.001, CA vs HV p&amp;lt;0.001). After adjustment for intracellular volume the MBF in patients with CA remained significantly lower than in HV (stress MBF/ICV: AL = 2.24±1.12, ATTR = 2.22±0.93, HV = 4.38±1.06; AL vs. ATTR p=1.000, AL vs HV p&amp;lt;0.001, ATTR vs. HV p&amp;lt;0.001). Myocardial perfusion reserve (MPR) was severely reduced in CA patients, compared to HV and patients with unobstructed coronary arteries, with the degree of reduction being comparable only to patients with 3VD (CA = 1.55±0.60, 3VD = 1.54±0.51, unobstructed coronaries = 2.78±0.70, HV = 4.08±0.86; CA vs 3VD p=1.000, CA vs unobstructed coronary arteries p&amp;lt;0.001, CA vs. HV p&amp;lt;0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p&amp;lt;0.05). Biopsies demonstrated diffuse hypoxia with abnormal VEGF staining in cardiomyocytes and endothelial cells. Amyloid infiltration in intramural arteries was associated with severe lumen reduction in 20% of vessels, and severe reduction in capillary density. Conclusion CA is associated with severe myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia. Funding Acknowledgement Type of funding sources: None.

Coronary tortuosity in patients with acetylcholine-induced coronary microvascular spasm

Abstract Background Angina pectoris in the absence of relevant epicardial stenoses (ANOCA) is frequently caused by coronary microvascular spasm. It has been speculated that the morphology of epicardial coronary arteries is associated with microvascular spasm. One hypothesis is that the vasoconstriction of microvessels leads to intraluminal pressure increase in the vascular segments proximal to the spasm, which may shift the balance of vessel forces toward vessel elongation resulting in coronary tortuosity. Purpose We assessed the relationship between epicardial coronary tortuosity and coronary spasm to elucidate a potential relationship between structural and functional coronary abnormalities. Methods 610 patients (39% male, mean age 61 years) with stable angina yet unobstructed coronary arteries (&amp;lt;50% stenosis) were included in this study. All patients underwent invasive diagnostic coronary angiography followed by intracoronary acetylcholine (ACh) testing according to a standardized protocol. The ACh test was considered “positive” in the presence of (a) angina, ischemic ECG shifts during the test and ≥90% coronary diameter reduction (“epicardial spasm”) or (b) all above without epicardial spasm (“microvascular spasm”). Assessment of coronary tortuosity was performed using left and right coronary images in multiple projections in a blinded fashion. The number and angles of the coronary curves in late diastole determined the severity of coronary tortuosity previously defined by Eleid. Patients were divided into those with at least moderate tortuosity versus those with no or mild tortuosity. Results ACh-testing revealed epicardial spasm in 179 (29%) and microvascular spasm in 172 (28%) patients. The ACh-test was negative/inconclusive in the remaining 259 patients (43%). There were 298 patients (49%) with at least moderate coronary tortuosity. The remaining 312 patients had no or mild coronary tortuosity (51%). Patients with at least moderate tortuosity were more likely to have microvascular spasm (99 patients of 172 with microvascular spasm had at least moderate coronary tortuosity (58%) vs. 76 patients of 179 with epicardial spasm (43%) vs. 126 patients of 259 with negative/inconclusive ACh test (49%), p=0.017). Analysis of coronary tortuosity in patients with positive ACh-test showed that patients with at least moderate coronary tortuosity (n=175) had significantly more microvascular spasm (57%) than epicardial spasm (43%) (p=0.005). We also found that at least moderate coronary tortuosity was significantly more often found in patients with hypertension compared to patients without hypertension (230/438 vs. 71/172, p=0.015). Conclusions In this large cohort of ANOCA patients coronary tortuosity was associated with hypertension and microvascular spasm. Our results provide interesting insights into the relationship of coronary morphology and vasomotor function. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Berthold-Leibinger-Foundation, Ditzingen, Germany

Coronary microvascular dysfunction is associated with reduced cardiac performance in low flow low gradient aortic stenosis

Abstract Background Little is known about coronary microvascular function of patients with low-flow low-gradient aortic stenosis (LFLGAS). We hypothesized that LFLGAS is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac efficiency. Purpose To perform a prospective invasive assessment of CMD in patients with LFLGAS undergoing TAVI and to compare it with patients with NFHGAS. Moreover, we aimed to assess the possible acute impact of TAVI on coronary microvascular function and the interactions between CMD and of cardiac performance at speckle tracking echocardiography (STE). Methods Invasive thermodilution-based assessment was systematically performed in 41 consecutive patients with isolated severe AS with angiographic unobstructed coronary arteries undergoing TAVI. The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were derived to assess coronary microcirculatory function before and after TAVI. Advanced echocardiographic imaging, including STE, was performed to assess cardiac function. Results IMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 [14.6–39.1] vs 12.8 [8.6–19.2] p=0.002). Similarly, RRR was significantly lower in LFLGAS compared with NFHGAS (1.4 [1.1–2.1] vs 2.6 [1.5–3.3] p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index (rho=−0.427, p=0.005), low cardiac output (rho=−0.517, p=0.001), reduced peak atrial longitudinal strain (PALS) (rho=−0.610, p≤0.001) and presence of atrial fibrillation (54.6% vs 21.1%, p=0.036). Conversely, IMR was only modestly associated with the mean pressure aortic valve gradient (rho=−0.304, p=0.054). Notably, the mean gradient was significantly associated with IMR in the NFHGAS group (rho=0.632, p=0.003) but not in the LFLGAS (rho=−0.222, p=0.333). Similarly, high IMR was associated with the AVA in the NFHGAS group (rho=−0.50, p=0.025) but not in patients with LFLGAS (rho=0.157, p=0.497). Paradoxical LFLGAS emerged as a phenotype associated with CMD, poor left ventricular longitudinal systolic function and left atrial dysfunction. TAVI determined no significant variation in microvascular function (IMR: 16.0 [10.4–26.1] vs 16.6 [10.2–25.6], p=0.403) and in PALS (15.9 [9.9–26.5] vs 20.1 [12.3–26.7], p=0.222). Conversely, left ventricular global longitudinal strain increased overall after TAVI (−13.2 [8.4–16.6] vs −15.1 [9.4–17.8], p=0.047). Conclusions LFLGAS is associated with impaired coronary microvascular function compared with NFHGAS. Combined invasive assessment of microvascular function and advanced non-invasive imaging contributed to define different AS phenotypes. CMD was associated with low-flow state, left atrial dysfunction and reduced cardiac efficiency in patients with AS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott Vascular

Coronary Tortuosity as a New Phenotype for Ischemia without Coronary Artery Disease.

Coronary arteries tend to be more tortuous than other arteries and follow the repeated flexion and relaxation movements that occur during the cardiac cycle. Coronary tortuosity (CorT) leads to changes in coronary flow with a reduction in distal perfusion pressure, which could cause myocardial ischemia. To assess the association between CorT and myocardial ischemia. Between January 2015 and December 2017, 57 patients with angina and nonobstructive coronary artery disease detected by invasive coronary angiography (ICA) were retrospectively enrolled. Angiographic variables were analyzed to assess the presence and degree of tortuosity and correlated with their respective vascular territories on stress myocardial perfusion imaging (MPI). CorT was defined as coronary arteries with three or more bend angles ≤90°, measured during diastole. Statistical significance was determined at the 5% level. A total of 17 men and 40 women were enrolled (mean age 58.3 years). CorT was observed in 16 patients (28%) and in 24 of 171 arteries. There was a significant association between CorT and ischemia when analyzed per artery (p<0.0001). The angiographic factor most associated with ischemia was the number of bend angles in an epicardial artery measured at systole (p=0.021). This study showed an association of CorT and myocardial ischemia in patients with unobstructed coronary arteries and angina. An increased number of coronary bend angles measured by angiography during systole was related to ischemia.